Proton Pump Inhibitor Co-prescription, Dabigatran Use, and Ischaemic Stroke or Transient Ischaemic Attack in Atrial Fibrillation: A Population-Based Case-Control Study

Abstract

Background and Objectives: Proton pump inhibitors (PPIs) reduce gastric acidity and lower dabigatran plasma concentrations, raising concern about a clinically relevant drug–drug interaction. We examined whether PPI co-prescription modified the association between dabigatran use and atrial fibrillation (AF)-associated ischaemic stroke (IS) or transient ischaemic attack (TIA). Methods: We conducted a population-based case-control study of adults with AF in Auckland, New Zealand. Cases were patients with adjudicated IS/TIA between September 2020 and August 2021 identified from the fifth Auckland Regional Community Stroke Study, which uses multiple overlapping ascertainment sources and independent clinical adjudication. Controls were patients with AF from the same source population who remained free of IS/TIA during the surveillance period, sampled from the Ministry of Health National Minimum Dataset. Individual-level demographics, comorbidities and medication exposures were obtained from electronic clinical records and dispensing data. Multivariable logistic regression included dabigatran use, PPI use and their interaction term, with adjustment for pre-specified clinical covariates. Results: The analytic sample comprised 300 IS/TIA cases and 1,608 controls. Dabigatran use was associated with lower odds of IS/TIA (adjusted odds ratio [aOR] 0.36 [95%CI 0.24–0.53]). PPI use was associated with higher odds of IS/TIA (aOR 1.55 [95%CI 1.08–2.24]), but this association is likely subject to residual confounding and should not be interpreted as causal. The dabigatran × PPI interaction was not statistically significant (aOR 0.98 [95%CI 0.57–1.69]; p = 0.94). Conclusion: We found no evidence of a large dabigatran-specific interaction with PPI co-prescription. These findings do not support a major clinically important attenuation of dabigatran’s association with lower odds of AF-associated IS/TIA, although modest effect modification cannot be excluded. Generalisability to lower-risk primary-care AF populations and healthcare systems with different patient characteristics may be limited.